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simeprevir 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
Hepatitis Virus C (HVC) protease inhibitors	4812	923604-59-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: olysio TMC-435 TMC435350 simeprevir simeprevir sodium	Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS. Molecular weight: 749.94 Formula: C38H47N5O7S2 CLOGP: 5.45 LIPINSKI: 3 HAC: 12 HDO: 2 TPSA: 156.89 ALOGS: -5.39 ROTB: 7 Status: OFM Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

olysio
TMC-435
TMC435350
simeprevir
simeprevir sodium

Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS.

Molecular weight: 749.94
Formula: C38H47N5O7S2
CLOGP: 5.45
LIPINSKI: 3
HAC: 12
HDO: 2
TPSA: 156.89
ALOGS: -5.39
ROTB: 7

Status: OFM

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.15	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Hosey CM, Chan R, Benet LZ

Approvals:

Date	Agency	Company	Orphan
May 14, 2014	EMA
Nov. 22, 2013	FDA	JANSSEN PRODS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Platelet count decreased	773.97	36.36	301	4456	106082	56181228
Anaemia	573.80	36.36	325	4432	267186	56020124
White blood cell count decreased	464.65	36.36	221	4536	125769	56161541
Blood bilirubin increased	388.10	36.36	134	4623	33220	56254090
Hepatitis C	290.98	36.36	72	4685	5514	56281796
Neutrophil count decreased	277.54	36.36	117	4640	49705	56237605
Haemoglobin decreased	217.43	36.36	137	4620	134000	56153310
Hyperbilirubinaemia	166.27	36.36	53	4704	10182	56277128
Haemolytic anaemia	148.49	36.36	48	4709	9637	56277673
Hepatocellular carcinoma	105.47	36.36	27	4730	2362	56284948
Pruritus	101.79	36.36	129	4628	316494	55970816
Off label use	94.57	36.36	168	4589	556012	55731298
Pyrexia	91.90	36.36	142	4615	418631	55868679
Photosensitivity reaction	85.86	36.36	35	4722	13558	56273752
Remission not achieved	51.97	36.36	9	4748	113	56287197
Decreased appetite	45.94	36.36	73	4684	219158	56068152
Hepatic failure	43.74	36.36	30	4727	33456	56253854
Hepatic function abnormal	42.88	36.36	30	4727	34528	56252782
Jaundice	41.79	36.36	27	4730	27267	56260043
Hepatic encephalopathy	40.82	36.36	19	4738	10091	56277219
Sunburn	40.44	36.36	13	4744	2555	56284755
Hepatitis C RNA increased	37.55	36.36	7	4750	136	56287174
Pain	36.90	36.36	6	4751	663178	55624132

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hepatitis C	769.03	29.92	207	5476	10423	31681238
Platelet count decreased	542.28	29.92	300	5383	110135	31581526
White blood cell count decreased	391.37	29.92	224	5459	87174	31604487
Blood bilirubin increased	352.96	29.92	156	5527	34980	31656681
Anaemia	306.54	29.92	273	5410	213249	31478412
Hepatocellular carcinoma	240.55	29.92	81	5602	8675	31682986
Off label use	193.76	29.92	271	5412	347003	31344658
Hyperbilirubinaemia	170.95	29.92	74	5609	15676	31675985
Haemoglobin decreased	144.73	29.92	136	5547	112539	31579122
Neutrophil count decreased	142.91	29.92	94	5589	46300	31645361
Photosensitivity reaction	139.30	29.92	56	5627	9848	31681813
Drug ineffective	90.62	29.92	210	5473	395363	31296298
Jaundice	73.38	29.92	53	5630	30234	31661427
Remission not achieved	71.07	29.92	13	5670	100	31691561
Pruritus	67.92	29.92	97	5586	125070	31566591
Haemolytic anaemia	59.83	29.92	31	5652	9765	31681896
Sunburn	51.50	29.92	17	5666	1703	31689958
Treatment failure	47.89	29.92	47	5636	40745	31650916
Hepatic failure	46.68	29.92	42	5641	32660	31659001
Genotype drug resistance test positive	45.88	29.92	14	5669	1087	31690574
Pyrexia	44.43	29.92	137	5546	303703	31387958
Viral load increased	43.74	29.92	16	5667	2173	31689488
Hepatitis C RNA increased	42.86	29.92	10	5673	274	31691387
Hepatic encephalopathy	42.71	29.92	28	5655	13643	31678018
Ascites	42.19	29.92	44	5639	40969	31650692
Thought blocking	38.68	29.92	8	5675	123	31691538
Bilirubin conjugated increased	38.13	29.92	16	5667	3125	31688536
Rash	34.27	29.92	96	5587	201390	31490271
Choroiditis	33.13	29.92	11	5672	1121	31690540
Hyperuricaemia	32.84	29.92	19	5664	7419	31684242

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Platelet count decreased	1363.06	30.23	600	9114	177622	70741108
Hepatitis C	940.26	30.23	239	9475	12568	70906162
White blood cell count decreased	897.17	30.23	444	9270	169697	70749033
Anaemia	855.84	30.23	581	9133	402842	70515888
Blood bilirubin increased	692.15	30.23	272	9442	59629	70859101
Neutrophil count decreased	414.53	30.23	210	9504	83346	70835384
Haemoglobin decreased	365.24	30.23	267	9447	204892	70713838
Hepatocellular carcinoma	346.11	30.23	104	9610	10104	70908626
Hyperbilirubinaemia	315.56	30.23	118	9596	22450	70896280
Haemolytic anaemia	202.99	30.23	79	9635	16715	70902015
Pruritus	153.12	30.23	211	9503	345349	70573381
Photosensitivity reaction	139.49	30.23	63	9651	19277	70899453
Pyrexia	136.64	30.23	273	9441	606679	70312051
Jaundice	109.07	30.23	74	9640	50034	70868696
Remission not achieved	104.54	30.23	21	9693	369	70918361
Off label use	89.84	30.23	263	9451	742797	70175933
Hepatic failure	84.38	30.23	67	9647	57558	70861172
Hepatic encephalopathy	66.32	30.23	40	9674	22078	70896652
Hepatitis C RNA increased	63.47	30.23	14	9700	392	70918338
Bilirubin conjugated increased	61.25	30.23	24	9690	5157	70913573
Rash	59.80	30.23	179	9535	510383	70408347
Pain	59.43	30.23	8	9706	628808	70289922
Ascites	56.01	30.23	57	9657	67490	70851240
Hyperuricaemia	55.45	30.23	28	9686	10938	70907792
Sunburn	54.73	30.23	20	9694	3551	70915179
Decreased appetite	53.10	30.23	124	9590	304656	70614074
Insomnia	47.45	30.23	97	9617	217709	70701021
Malaise	47.08	30.23	148	9566	432784	70485946
Hepatorenal syndrome	45.61	30.23	18	9696	3939	70914791
Aspartate aminotransferase increased	45.01	30.23	70	9644	126908	70791822
Hepatic function abnormal	41.76	30.23	49	9665	67947	70850783
Red blood cell count decreased	41.39	30.23	43	9671	52118	70866612
Hepatic cirrhosis	41.29	30.23	34	9680	30697	70888033
Thought blocking	37.53	30.23	8	9706	190	70918540
Viral load increased	37.48	30.23	14	9700	2642	70916088
Choroiditis	34.54	30.23	11	9703	1290	70917440
Liver disorder	33.93	30.23	42	9672	61526	70857204
Alanine aminotransferase increased	32.46	30.23	66	9648	147414	70771316
Injection site dermatitis	31.64	30.23	5	9709	19	70918711
Incorrect product administration duration	30.96	30.23	19	9695	10805	70907925

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	J05AP05	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000998	Antiviral Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D011480	Protease Inhibitors
FDA MoA	N0000182138	Cytochrome P450 1A2 Inhibitors
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA MoA	N0000182638	HCV NS3/4A Protease Inhibitors
FDA EPC	N0000182639	Hepatitis C Virus NS3/4A Protease Inhibitor
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190107	Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA	N0000190108	Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors
FDA MoA	N0000193845	Bile Salt Export Pump Inhibitors
FDA MoA	N0000193960	Multidrug Resistance-Associated Protein 2 Inhibitors
FDA MoA	N0000193965	Sodium Taurocholate Co-transporting Polypeptide Inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Chronic hepatitis C	indication	128302006

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.35	acidic
pKa2	6.66	Basic
pKa3	3.5	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8349869	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8741926	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8754106	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9040562	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9353103	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9623022	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9856265	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8148399	Sept. 5, 2029	METHOD OF TREATING HEPATITIS C

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Cathepsin S	Enzyme	P25774	CATS_HUMAN		IC50	6.10	CHEMBL
Hepatitis C virus serine protease, NS3/NS4A	Enzyme		A3EZI9_9HEPC D2K2A8_9HEPC	INHIBITOR	Ki	9.30	CHEMBL	CHEMBL
Genome polyprotein	Polyprotein		POLG_HCVH	INHIBITOR	Ki	9.44	SCIENTIFIC LITERATURE	DRUG LABEL
Polyprotein	Polyprotein		Q6GYR8_9HEPC	INHIBITOR	Ki	9.44	IUPHAR
Nonstructural protein NS3-4A	Unclassified		A0A0K1CY61_9HEPC		Ki	9.44	CHEMBL
Genome polyprotein	Unclassified		A3EZJ3_9HEPC		Ki	9.30	CHEMBL

External reference:

ID	Source
D10081	KEGG_DRUG
4032900	VANDF
CHEBI:134743	CHEBI
30B	PDB_CHEM_ID
CHEMBL501849	ChEMBL_ID
7367	IUPHAR_LIGAND_ID
9432	INN_ID
1241946-89-3	SECONDARY_CAS_RN
DB06290	DRUGBANK_ID
9WS5RD66HZ	UNII
1482790	RXNORM
207569	MMSL
29896	MMSL
d08182	MMSL
015309	NDDF
015310	NDDF
708823009	SNOMEDCT_US
714167009	SNOMEDCT_US
C2605855	UMLSCUI
D000069616	MESH_DESCRIPTOR_UI
CHEMBL3137358	ChEMBL_ID
24873435	PUBCHEM_CID

Pharmaceutical products:

None